“Food allergy has become an epidemic worldwide,” Soheila Maleki of USDA- Agricultural Research Service said during a session presentation titled—Effects of Cross-Reactivity in Food Allergy Detection & Diagnosis—during Pittcon 2016 in Atlanta last week.

USDA studies estimate that more than 15 million people have food allergies. Of that number, 6 million are allergic to shellfish, and 3 million allergic to peanuts and tree nuts.

“The number of people who have allergies has tripled over the past 10 years,” Maleki added.

For this reason, the government agency has taken up a study focused on improving detection, diagnosis and therapeutics by trying to determine the difference between clinically relevant and irrelevant IgE (allergy) antibody binding to multiple allergens in peanuts and tree nuts.

According to previous research, if a person is allergic to a particular food, he or she is more likely to be allergic to another food. Maleki stated that if a person is clinically symptomatic (has a reaction) to peanut and walnut, for example, then this person had clinically relevant cross-reactivity. However, if that same person, who has IgE to peanut and walnut, also has IgE antibody to pistachio and almond, but can still eat these nuts and have no reaction, then that’s clinically irrelevant cross-reactivity. So while this person could have antibody cross-reactivity, he/she doesn’t have clinical cross-reactivity.

“A single antibody, with a single specificity (monoclonal) is thought to be highly specific for its target binding site (binds to nothing else or very little than its target),” Maleki explained to R&D Magazine post-session. “Similar to when a key fits a lock. For example, you don’t really expect your key to open a neighbor’s front door. It’s monoclonal or monospecific, specific only for your front door.”

In the case of the human IgE antibody, which mediates the allergic response in food allergy, it’s polyclonal (a population of IgE). In other words, several keys (antibodies) bind to a group of targets sometimes on the same molecule. This response is similar to having five keys (antibodies) to your house (one molecule). So regardless of the fact that your neighbor has eight keys (monoclonal IgEs), none will open your or anyone else’s door (allergic molecules). So in theory, if an allergic person has IgE to one allergic molecule, he/she may have 10 different kinds of IgE to that molecule, but none of these antibodies should recognize different molecules, because they should be specific for that molecule (door), Maleki added.

However, the government study has found this theory is untrue—a single IgE molecule can bind to multiple allergens because it happens to have a very similar string of amino acid sequences that the antibodies deem to be the same. The research team used computational methods to predict IgE environments, mainly a software tool SDAP database to help show where the peptides (string of amino acids) are located in a molecule. The study hypothesizes that there are repeat amino acid sequences that human antibodies recognize among multiple peanut and tree nut allergens that are also recognized by human serum IgE, which are thought to be responsible for clinically relevant IgE binding.

To examine the food allergy dynamic closer, USDA-ARS made monoclonal antibodies against Ara h 2 (the dominant peanut allergen detected in most patients) that overlap with IgE binding sites and showed that these antibodies do indeed cross-react with other allergic molecules, confirming the agency’s repeat-sequence hypothesis, according to Maleki. Repeat sequences may be clinically relevant in IgE.

The team also synthesized synthetic peptides that represent about 30 whole allergen molecules (proteins) from peanut and tree nut, which was incubated with peanut or tree nut allergic allergens that are targeted or recognized by IgE molecules.

“We are not sure what will come out of this work without looking at more patient sera IgE binding to our peptides and statistical analysis of the data,” Maleki told R&D. “However we believe that either antibody specificity or promiscuity patterns will emerge and the repeated sequences will contribute to either clinically relevant or irrelevant IgE binding.”

 

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